Experimental neurology
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Experimental neurology · Sep 2008
Clinical TrialLocal field potential beta activity in the subthalamic nucleus of patients with Parkinson's disease is associated with improvements in bradykinesia after dopamine and deep brain stimulation.
Parkinson's disease is treated pharmacologically with dopamine replacement medication and, more recently, by stimulating basal-ganglia nuclei such as the subthalamic nucleus (STN). Depth recordings after this procedure have revealed excessive activity at frequencies between 8 and 35 Hz (Brown et al., 2001; Kuhn et al., 2004; Priori et al., 2004) that are reduced by dopamine therapy in tandem with improvements in bradykinesia/rigidity, but not tremor (Kuhn et al., 2006). It has also been shown that improvements in motor symptoms after dopamine correlate with single unit activity in the beta range (Weinberger et al., 2006). ⋯ As well as replicating Kuhn et al., using the same patients we were able to extend Weinberger et al. to show that LFP beta oscillatory activity correlated with the degree of improvement in bradykinesia/rigidity, but not tremor, after dopamine medication. We also found that the power of beta oscillatory activity uniquely predicted improvements in bradykinesia/rigidity, but again not tremor, after stimulation of the STN in a regression analysis. However improvements after STN stimulation related inversely to beta power, possibly reflecting the accuracy of the electrode placement and/or the limits of STN stimulation in patients with the greatest levels of beta oscillatory activity.
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Experimental neurology · Sep 2008
Midline brain injury in the immature rat induces sustained cognitive deficits, bihemispheric axonal injury and neurodegeneration.
Infants and children less than 4 years old suffer chronic cognitive deficits following mild, moderate or severe diffuse traumatic brain injury (TBI). It has been suggested that the underlying neuropathologic basis for behavioral deficits following severe TBI is acute brain swelling, subarachnoid hemorrhage and axonal injury. To better understand mechanisms of cognitive dysfunction in mild-moderate TBI, a closed head injury model of midline TBI in the immature rat was developed. ⋯ Between 6 and 72 h, blood-brain barrier breakdown, extensive traumatic axonal injury in the subcortical white matter and thalamus, and focal areas of neurodegeneration in the cortex and hippocampus were observed in both hemispheres of the injured brain. At 8 to 18 days post-injury, reactive astrocytosis in the cortex, axonal degeneration in the subcortical white matter tracts, and degeneration of neuronal cell bodies and processes in the thalamus of both hemispheres were observed; however, cortical volumes were not different between un-injured and injured rat brains. These data suggest that diffuse TBI in the immature rat can lead to ongoing degeneration of both cell soma and axonal compartments of neurons, which may contribute, in part, to the observed sustained cognitive deficits.
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Experimental neurology · Aug 2008
Magnetic resonance imaging of mouse skeletal muscle to measure denervation atrophy.
We assessed the potential of different MRI measures to detect and quantify skeletal muscle changes with denervation in two mouse models of denervation/neurogenic atrophy. Acute complete denervation and chronic partial denervation were examined in calf muscles after sciatic nerve axotomy and in transgenic SOD1(G93A) mice, respectively. Serial T(2), diffusion tensor, and high resolution anatomical images were acquired, and compared to behavioral, histological, and electrophysiological data. ⋯ Changes in T(2) and muscle volume were first observed in medial gastrocnemius and later in other calf muscles. Alterations in secondary and tertiary eigenvalues obtained from DTI were first observed in tibialis anterior and medial gastrocnemius muscles at age 12 weeks. We propose that MRI of skeletal muscle is a sensitive surrogate outcome measure of denervation atrophy in animal models of neuromuscular disorders, with potential applicability in preclinical therapeutic screening studies in rodents.
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Experimental neurology · Aug 2008
BDNF induces late-phase LTP of C-fiber evoked field potentials in rat spinal dorsal horn.
Several lines of evidence have shown that in some brain regions brain-derived neurotrophic factor (BDNF) is important for long-term potentiation (LTP), a synaptic model of memory storage. In the present work we evaluate the role of BDNF in LTP of C-fiber evoked field potentials in spinal dorsal horn, a synaptic model of pain memory. We found that spinal application of BDNF-induced LTP of C-fiber evoked field potentials with a long latency, lasting for >8 h, and the effect was blocked by either tyrosine kinase inhibitor (K252a) or BNDF scavenger (TrkB-Fc). ⋯ BDNF-induced LTP was completely abolished by the protein synthesis inhibitor (anisomycin), by N-methyl-D-aspartate (NMDA) receptor blocker (MK-801), by extracellular signal-regulated protein kinase (ERK) inhibitor (PD98059) or by p38 mitogen-activated protein kinase (MAPK) inhibitor (SB203580) but not by c-Jun N-terminal kinase (JNK) inhibitor (SP600125). Nuclear factor-kappaB (NF-kappaB) inhibitor (PDTC) also suppressed spinal BDNF-LTP. The results suggest that BDNF play a crucial role in protein synthesis-dependent L-LTP in spinal dorsal horn via activation of ERK, p38 MAPK and NF-kappaB signal pathways.
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Experimental neurology · Aug 2008
Late expression of Na+/H+ exchanger 1 (NHE1) and neuroprotective effects of NHE inhibitor in the gerbil hippocampal CA1 region induced by transient ischemia.
Although acidosis may be involved in neuronal death, the participation of Na(+)/H(+) exchanger (NHE) in delayed neuronal death in the hippocampal CA1 region induced by transient forebrain ischemia has not been well established. In the present study, we investigated the chronological alterations of NHE1 in the hippocampal CA1 region using a gerbil model after ischemia/reperfusion. In the sham-operated group, NHE1 immunoreactivity was weakly detected in the CA1 region. ⋯ In addition, NHE inhibitor potently protected CA1 pyramidal neurons from ischemic damage, and NHE inhibitor attenuated the activation of astrocytes and microglia in the ischemic CA1 region. In addition, NHE inhibitor treatment blocked Na(+)/Ca(2+) exchanger 1 immunoreactivity in the CA1 region after transient forebrain ischemia. These results suggest that NHE1 may play a role in the delayed death, and the treatment with NHE inhibitor protects neurons from ischemic damage.